Significance of retrograde diastolic uterine artery blood flow during regional anesthesia in instrumented pregnant sheep.

BACKGROUND: We studied the interactions between uterine and placental hemodynamics during maternal hypotension in chronically instrumented fetal sheep. In addition, we investigated maternal hemodynamic characteristics, fetoplacental hemodynamics and fetal acid-base status when a retrograde diastolic uterine artery blood flow pattern is present during maternal hypotension. METHODS: Invasive maternal and fetal hemodynamic parameters, uterine (Q(UtA)) and placental (Q(UA)) volume blood flows and acid-base values were examined in 24 chronically instrumented sheep at baseline and during epidural-induced maternal hypotension at 117-132 (term 145) days of gestation. Uterine artery blood flow velocity waveforms were obtained by Doppler ultrasonography. RESULTS: Maternal hypotension decreased Q(UtA) without affecting Q(UA). During hypotension, eight out of 24 sheep demonstrated a retrograde diastolic blood flow velocity waveform pattern in the uterine artery. Maternal systolic, diastolic and mean arterial blood pressures were significantly lower in the retrograde group than in the antegrade group. No statistically significant differences in Q(UtA), Q(UA) and fetal blood gas values were detected between the two groups during hypotension. CONCLUSIONS: An acute decrease in uterine artery volume blood flow during maternal hypotension is not compensated by increased placental volume blood flow. A retrograde diastolic blood flow pattern in the uterine artery is related to lower maternal arterial pressures, especially during diastole. A uterine artery retrograde diastolic blood flow pattern does not have any additional detrimental short-term effects on fetal acid-base status.

Divergent effects of ephedrine and phenylephrine on cardiovascular hemodynamics of near-term fetal sheep exposed to hypoxemia and maternal hypotension.

BACKGROUND: We hypothesized that the administration of ephedrine and phenylephrine for maternal hypotension modifies cardiovascular hemodynamics in near-term sheep fetuses. METHODS: At 115-136 days of gestation, chronically instrumented, anesthetized ewes with either normal placental function or increased placental vascular resistance after placental embolization were randomized to receive boluses of ephedrine (n = 12) or phenylephrine (n = 12) for epidural-induced hypotension after a short period of hypoxemia. Fetal cardiovascular hemodynamics were assessed by Doppler ultrasonography at baseline, during hypotension and after vasopressor treatment. RESULTS: During hypotension, fetal PO(2) decreased and proximal branch pulmonary arterial and pulmonary venous vascular impedances increased. Additionally, in the embolized fetuses, the time-velocity integral ratio between the antegrade and retrograde blood flow components of the aortic isthmus decreased. These parameters were restored to baseline conditions by ephedrine but not by phenylephrine. With phenylephrine, weight-indexed left ventricular cardiac output and ejection force decreased in the non-embolized fetuses, and the proportion of isovolumetric contraction time of the total cardiac cycle was elevated in the embolized fetuses. CONCLUSIONS: After exposure to hypoxemia and maternal hypotension, ephedrine restored all fetal cardiovascular hemodynamic parameters to baseline. Phenylephrine did not reverse fetal pulmonary vasoconstriction or the relative decrease in the net forward flow through the aortic isthmus observed in fetuses with increased placental vascular resistance. Moreover, fetal left ventricular function was impaired during phenylephrine administration.

Experimental validation of uterine artery volume blood flow measurement by Doppler ultrasonography in pregnant sheep.

OBJECTIVE: To test the hypothesis that Doppler-derived (calculated) uterine artery volume blood flow (cQ(UtA)) reflects accurately volume blood flow measured directly (mQ(UtA)) in an experimental setting. METHODS: Five pregnant sheep were instrumented at 122-130 days of gestation under general anesthesia. After a 4-day recovery period, maternal hemodynamics were varied by administering to the sheep under general anesthesia noradrenaline, beta-blocker, low oxygen gas mixture, epidural bupivacaine and ephedrine, consecutively. The central venous pressure was obtained with the help of a thermodilution catheter. The mean arterial pressure and acid-base status were monitored using a 16-gauge polyurethane catheter inserted into the descending aorta via a femoral artery. A 6-mm transit-time ultrasonic perivascular flow probe was used to measure the mQ(UtA). Doppler ultrasonography of the uterine artery was performed and volume blood flow was obtained simultaneously by the transit-time ultrasonic perivascular flow probe during each phase of the experiment. RESULTS: A total of 31 observations were made. The mQ(UtA) varied between 90 and 800 (mean +/- SD, 419 +/- 206) mL/min during the experiments. The corresponding values for the cQ(UtA) were 110 and 900 (mean +/- SD, 459 +/- 211) mL/min. There was a significant correlation (R = 0.76; P < 0.0001) between mQ(UtA) and cQ(UtA). The mQ(UtA) correlated positively with Doppler-derived uterine artery absolute velocities, i.e. peak systolic (R = 0.50; P = 0.004), end-diastolic (R = 0.53; P = 0.002) and time-averaged maximum (R = 0.69; P < 0.0001) and time-averaged intensity weighted mean (R = 0.75; P < 0.0001) velocities. CONCLUSION: cQ(UtA) correlates well with volume blood flow measured directly. Doppler-derived uterine artery absolute blood flow velocities reflect uteroplacental volume blood flow in pregnant sheep. Published by John Wiley & Sons, Ltd.

Ephedrine and phenylephrine for the treatment of maternal hypotension in a chronic sheep model of increased placental vascular resistance.

BACKGROUND: We hypothesized that ephedrine and phenylephrine are equal with respect to uterine and placental haemodynamics and fetal acid-base status after exposure to maternal hypoxaemia and hypotension in a chronic sheep model of increased placental vascular resistance (R(UA)). METHODS: At 114-135 days gestation, chronically instrumented fetal sheep underwent placental embolization leading to increased R(UA). Twenty-four hours after embolization, the ewes were anaesthetized and randomized to receive boluses of ephedrine (n=7) or phenylephrine (n=6) for epidural-induced hypotension after maternal hypoxaemia. Uterine (Q(UtA)) and placental (Q(UA)) volume blood flows and uterine vascular resistance (R(UtA)) and R(UA) were recorded. Uterine (PI(UtA)) and umbilical artery (PI(UA)) pulsatility indices were obtained by Doppler ultrasonography. Fetal arterial blood samples were analysed for acid-base values and lactate concentrations. RESULTS: During hypotension, Q(UtA), fetal pH, BE, and Po(2) decreased whereas R(UtA), PI(UtA), R(UA), and fetal lactate concentration increased. With ephedrine, Q(UtA), R(UtA), PI(UtA), R(UA), and fetal Po(2) returned to baseline. Fetal pH, BE, and lactate concentration did not change from hypotensive values. With phenylephrine, Q(UtA) remained lower (P=0.007) and R(UtA) (P=0.007), PI(UtA) (P=0.013), and R(UA) (P=0.050) higher than at baseline. Fetal Po(2) returned to baseline and fetal pH and BE did not change from hypotensive values. However, fetal lactate concentration increased further (mean difference 1.49, 95% confidence interval 0.72-2.26 mmol litre(-1); P=0.004). CONCLUSIONS: In a chronic sheep model of increased placental vascular resistance, compared with ephedrine administration, phenylephrine administration was associated with impaired uterine and placental haemodynamics and increased fetal lactate concentrations.

Effects of ephedrine and phenylephrine on uterine and placental circulations and fetal outcome following fetal hypoxaemia and epidural-induced hypotension in a sheep model.

BACKGROUND: Recent studies support the use of alpha-agonists during regional anaesthesia in uncomplicated term pregnancies. We hypothesized that ephedrine and phenylephrine, administered for maternal hypotension following fetal hypoxaemia, are equal in respect of fetal outcome. METHODS: At 117-132 days gestation, chronically instrumented, anaesthetized and mechanically ventilated ewes were randomized to receive boluses of ephedrine (n=9) or phenylephrine (n=8) for maternal epidural-induced hypotension after a period of fetal hypoxaemia. Uterine (QUtA) and placental (QUA) volume blood flows were measured with perivascular transit-time ultrasonic flow probes, and uterine (RUtA) and placental (RUA) vascular resistances were computed from volume blood flows and maternal and fetal mean arterial pressures. Uterine (PIUtA) and umbilical artery (PIUA) pulsatility indices were obtained by Doppler ultrasonography. RESULTS: Ephedrine increased QUtA and decreased RUtA and PIUtA from a hypotensive to baseline level and had no significant effect on umbilical circulation. With phenylephrine, QUtA remained lower (P=0.011) and RUtA higher (P=0.043) than at baseline, although PIUtA decreased to baseline level. PIUA increased from baseline with phenylephrine (P=0.007), whereas QUA decreased (P=0.050). Maternal volume expansion with hydroxyethyl starch decreased RUtA significantly irrespective of the vasopressor used. There were no significant differences in fetal blood gas values or lactate concentrations between the ephedrine and phenylephrine groups. CONCLUSIONS: Despite the more favourable effects on uterine and placental circulations of ephedrine over phenylephrine, no significant differences in fetal acid-base status or lactate concentrations were observed.